In the small preterm infants, patent ductus arteriosus (PDA) is a common and often serious concomitant of respiratory distress syndrome (RDS). Recently indomethacin has been proposed as a potentially useful pharmacologic agent for inducing ductal closure in these infants. Early investigations of this technique have yielded conflicting results, both as to efficacy and safety of this drug. Since no single institution has enough small prematures to allow for a conclusive trial, within a reasonable period of time, a collaborative trial among 12 institutions was instituted in October, 1978, with the avowed goal of enrolling, within one year, 2000 infants weighing less than or equal to 1750 grams. Among these we estimated 400 to have significant PDA and to be the subjects of a clinical trial evaluating the effectiveness and safety of indomethacin treatment, per se, and relative to surgery. The outcome variables to be studied include hospital mortality, duration of ventilatory support, length of hospitalization, and incidence of complications (necrotizing enterocolitis, apnea/bradycardia, etc.). A follow-up evaluation at one year of age of all survivors who had PDA and a subset of infants without PDA will be carried out to elucidate the effects of PDA and its management on the cardiovascular, pulmonary, neurologic, renal, and general developmental status of these babies. Finally, by utilizing data from the entire cohort, we will be able to evaluate a variety of perinatal factors as determinants of the occurrence of PDA.